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Updated: Oct 12, 2025

Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay
Published on: June 30, 2023
Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway
Amjad Husain1, Arogya Khadka2, Allen Ehrlicher3
1Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Innovation and Incubation Centre for Entrepreneurship, IISER, Bhopal, MP, 462066, India; Centre for Science and Society, IISER, Bhopal, MP, 462066, India.
Abstract:
While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.
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